The vertebrate immune responses to infectious agents are regulated and mediated by T lymphocytes. The primary event in this immune induction is a recognition of foreign antigenic determinants by a receptor present in the plasma membrane of the T cell. The aims of this proposal focus on the molecular properties of the T cell antigen receptor, and hence of the basis of antigen-specific immunity. In order to investigate the structure of the T cell receptor, a recombinant DNA clone we recently isolated will be used to isolate cDNA clones from T cell hybridomas of defined specificity for antigen and major histocompatibility complex (MHC) molecules. A comparison of the sequence of the receptor genes from these cell lines will be carried out in order to understand how the receptor simultaneously distinguishes differences in both antigen and MHC determinants. A second aim of this proposal is to investigate the maturation of T cells with respect to the ontogeny of receptor expression, focusing on the stage at which receptor expression first occurs, and on the levels of receptor expression at the different stages of T cell maturation. The importance of these experiments relates to mechanisms of T cell selection for self and nonself recognition. Further experiments proposed are designed to facilitate the isolation of antibodies specific for the constant region of the T cell receptor. These experiments will take advantage of a procaryotic expression vector to produce an immunogenic polypeptide containing the entire constant region of the receptor. Using recombinant DNA techniques the experiments described in this proposal will address several of the fundamental questions concerning T cell biology, questions not previously approachable prior to the molecular cloning of T cell receptor genes.